Drug addiction and abuse exacts a heavy toll on society, the health care system, and the economy. A therapy that allows the rapid, effective neutralization of addictive drugs in vivo would enjoy extensive use. Studies in the 1970's showed that conventional antibodies could block heroin's effects in addicted monkeys, but these antibodies had slow kinetics and were effective only with low doses of the addictive substance. However, some catalytic antibodies have exhibited kinetics similar to naturally occurring enzymes and, therefore, could prove effective in treating drug addiction. In the proposed research studies, research collaborators at The Scripps Research Institute will generate antibodies that selectively degrade cocaine via ester hydrolysis. Then hybridomas secreting these antibodies will be identified and isolated using One Cell Systems' proprietary gel microdrop (GMD) secretion assay combined with fluorescent activated cell sorting (FACS). The GMD technology is ideally suited to isolating rare hybridomas that are expected to produce relatively small amounts of the desired catalytic antibodies. Development of pharmacotherapies for substances of abuse are urgently needed. PROPOSED COMMERCIAL APPLICATION: Isolation of cocaine specific catalytic antibodies for systemic in vivo administration would have significant therapeutic utility. The novel assay and recovery method is expected to have wide utility for discovery of a variety of catalytic antibodies for therapeutic as well as industrial use.